Radiometallic Complexes of DO3A-Benzothiazole Aniline for Nuclear Medicine Theranostics

• Published in: Molecular pharmaceutics 2018-03, Vol.15 (3), p.1133-1141
• Main Authors: Park, Ji-Ae, Lee, Ji Woong, Kim, Hee-Kyung, Shin, Un Chol, Lee, Kyo Chul, Kim, Tae-Jeong, Chang, Yongmin, Kim, Kyeong Min, Kim, Jung Young, Lee, Yong Jin
• Format: Article
• Language: English
• Subjects: Aniline Compounds - administration & dosage; Aniline Compounds - chemistry; Animals; Benzothiazoles - administration & dosage; Benzothiazoles - chemistry; Copper Radioisotopes - administration & dosage; Copper Radioisotopes - chemistry; Female; Gallium Radioisotopes - administration & dosage; Gallium Radioisotopes - chemistry; HEK293 Cells; HeLa Cells; Heterocyclic Compounds, 1-Ring - administration & dosage; Heterocyclic Compounds, 1-Ring - chemistry; Humans; Lutetium - administration & dosage; Lutetium - chemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Positron-Emission Tomography - methods; Radioisotopes - administration & dosage; Radioisotopes - chemistry; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - chemistry; Theranostic Nanomedicine - methods; Treatment Outcome; Uterine Cervical Neoplasms - diagnostic imaging; Uterine Cervical Neoplasms - therapy; Xenograft Model Antitumor Assays
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.7b00996

To develop a radioactive metal complex platform for tumor theranostics, we introduced three radiopharmaceutical derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid-benzothiazole aniline (DO3A-BTA, L1) labeled with medical radioisotopes for diagnosis (68Ga/64Cu) and therapy (177Lu). The tumor-targeting ability of these complexes was demonstrated in a cellular uptake experiment, in which 177Lu-L1 exhibited markedly higher uptake in HeLa cells than the 177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex. According to in vivo positron emission tomography imaging, high accumulation of 68Ga-L1 and 64Cu-L1 was clearly visualized in the tumor site, while 177Lu-L1 showed therapeutic efficacy in therapy experiments. Consequently, this molecular platform represents a useful approach in nuclear medicine toward tumor-theranostic radiopharmaceuticals when 68Ga-L1 or 64Cu-L1 is used for diagnosis, 177Lu-L1 is used for therapy, or two of the compounds are used in conjunction with each other.